(115 days)
The Verigene® Staphylococcus Blood Culture (BC-S) Nucleic Acid Test performed using the sample-to-result Verigene System is a qualitative, multiplexed in vitro diagnostic test for the simultaneous detection and identification of potentially pathogenic gram-positive bacterial species Staphylococcus aureus ("SA") and Staphylococcus epidermidis ("SE") which may cause bloodstream infection (BSI). In addition, the BC-S test detects the mecA resistance marker inferring mecA-mediated methicillin/oxacillin resistance. In mixed growth, the BC-S Test does not specifically attribute mecA-mediated methicillin/oxacillin resistance to either SA or SE.
The BC-S test is performed directly on positive blood culture using BACTEC™ Plus Aerobic/F and BacT/ALERT FA FAN® Aerobic blood culture bottles, which contain gram-positive cocci in clusters (GPCCL) observed on Gram stain. Subculturing of positive blood cultures is necessary to recover organisms for susceptibility testing, differentiation of mixed growth, association of the mecA gene to an organism, or for epidemiological typing.
The BC-S test is indicated for use in conjunction with other clinical and laboratory findings, such as culture, to aid in the diagnosis of bacterial bloodstream infections; however, it is not used to monitor bloodstream infections.
The Verigene Staphylococcus Blood Culture Nucleic Acid Test (BC-S) is a molecular assay which relies on detection of specific nucleic acid targets in a microarray format. For each of the bacterial nucleic acid sequences detected by the BC-S test, Capture and Mediator oligonucleotides are utilized for gold nanoparticle probe-based endpoint detection. The Capture oligonucleotides bind to a specific portion of the nucleic acid target and are themselves bound onto a substrate in the microarray. The Mediator oligonucleotides bind to a different portion of the same nucleic acid target and allow binding of a gold nanoparticle probe to a portion complementary to a gold nanoparticle probe. Specific silver enhancement of the bound gold nanoparticle probes at the capture sites results in gold-silver aggregates that scatter light with high efficiency.
The BC-S test is performed on the Verigene System, a 'sample-to-result', fully automated, bench-top molecular diagnostics workstation. The Verigene System consists of two components: the Verigene Reader and the Verigene Processor SP. The BC-S test utilizes single-use disposable test consumables and a self-contained Verigene Test Cartridge for each sample tested. For the BC-S test, the Verigene System allows automated nucleic acid extraction from gram-positive bacteria-containing blood culture specimens and target detection of bacteria-specific DNA.
The Reader is the Verigene System's user interface, which serves as the central control unit for all aspects of test processing and results generation. The Reader's graphical user interface guides the user through test processing and test results using a barcode scanner.
The user inserts the Test Cartridge into the Verigene Processor SP, which executes the test procedure, automating the steps of ( ) Sample Preparation - Cell lysis and magnetic bead-based bacterial DNA isolation from blood culture samples and (2) Verigene Hybridization Test - Detection and identification of bacterial-specific DNA in a microarray format by using gold nanoparticle probe-based technology.
After test processing is complete, to obtain the test results the user removes the Test Cartridge from the Processor SP, removes the reagent pack from the substrate holder, and inserts the substrate holder into the Reader for analysis. Light scatter from the capture spots is imaged by the Reader and intensities from the microarray spots are used to make decisions regarding the presence (Detected) or absence (Not Detected) of a bacterial nucleic acid sequence/analyte.
This document describes the regulatory submission for the Verigene® Staphylococcus Blood Culture Nucleic Acid Test (BC-S) and its performance characteristics.
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1. Table of Acceptance Criteria and the Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" for the clinical performance in a pass/fail sense with numerical targets. However, the "Method Comparison Study" results can be interpreted as the device's reported performance against a reference standard. The goal implicitly is high agreement with the reference methods.
| Analyte | Performance Metric | Reported Device Performance |
|---|---|---|
| S. aureus | Sensitivity | 100% (97.1%-100% CI) |
| S. aureus | Specificity | 100% (98.2%-100% CI) |
| S. epidermidis | Sensitivity | 97.0% (91.2%-99.4% CI) |
| S. epidermidis | Specificity | 99.6% (97.6%-99.9% CI) |
| mecA gene | Sensitivity | 98.6% (94.6%-99.8% CI) |
| mecA gene | Specificity | 98.8% (93.4%-99.9% CI) |
2. Sample size used for the test set and the data provenance:
- Test Set Sample Size: 330 culture-positive, gram-positive (GPCCL) blood culture specimens from patients.
- Data Provenance:
- Country of Origin: Not explicitly stated, but the study was conducted at "five external clinical sites," implying clinical settings within a country, likely the US given the FDA submission.
- Retrospective or Prospective: Prospective, as subjects were "individuals receiving routine care requiring blood culture testing" and "specimens from these patients were identified for BC-S testing."
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Number of experts: Not explicitly stated.
- Qualifications of experts: The ground truth was established using "reference method results obtained from the standard biochemical bacterial detection and susceptibility techniques utilized in routine clinical practice." This implies standard microbiology laboratory personnel and practices, rather than a panel of individual experts.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- No explicit adjudication method is mentioned for the test set. The comparison was made against "reference method results obtained from the standard biochemical bacterial detection and susceptibility techniques utilized in routine clinical practice," suggesting a direct comparison rather than a consensus process.
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an in vitro diagnostic test for bacterial identification and resistance markers, not an imaging analysis tool that relies on human reader interpretation of images. The study focuses on the device's performance against standard microbiological methods.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, the performance data presented (analytical and clinical) represents the standalone performance of the Verigene® Staphylococcus Blood Culture Nucleic Acid Test (BC-S) and the Verigene® System. The system is described as a "sample-to-result, fully automated, bench-top molecular diagnostics workstation," implying minimal human intervention beyond setting up the test. The "Method Comparison Study" directly compares the device's output to standard laboratory results.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The ground truth used was reference method results obtained from standard biochemical bacterial detection and susceptibility techniques utilized in routine clinical practice. This essentially means the results from conventional microbiology tests (e.g., culture, biochemical identification, antimicrobial susceptibility testing) performed in clinical laboratories.
8. The sample size for the training set:
- The document does not explicitly state the sample size for a "training set." The performance data section focuses on "Analytical Testing" and "Clinical Testing" (Method Comparison Study, Reproducibility Study). In vitro diagnostic tests like this typically undergo extensive analytical validation (LOD, inclusivity, exclusivity, etc.) using characterized strains and then clinical validation with patient samples. The term "training set" is more common in machine learning contexts, which this device does not appear to primarily utilize in the same way. The strains used for "Analytical Reactivity (Inclusivity)" and "Analytical Specificity (Exclusivity)" could be considered part of developmental data but aren't explicitly called a training set.
9. How the ground truth for the training set was established:
- As a "training set" is not explicitly mentioned in the context of machine learning model training, the method for establishing its ground truth is not provided. However, the ground truth for the analytical validation (inclusivity/exclusivity) would have been established by standard microbiological characterization of the bacterial strains used (e.g., genetic sequencing, biochemical tests, culture).
§ 866.1640 Antimicrobial susceptibility test powder.
(a)
Identification. An antimicrobial susceptibility test powder is a device that consists of an antimicrobial drug powder packaged in vials in specified amounts and intended for use in clinical laboratories for determining in vitro susceptibility of bacterial pathogens to these therapeutic agents. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.(b)
Classification. Class II (performance standards).